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Page 2 of 10 Berezin. Vessel Plus 2018;2:22 I http://dx.doi.org/10.20517/2574-1209.2018.23
[4,5]
considerable regional differences in the prevalence of hypertension . Moreover, there is evidence that up
to 90% of all hypertensive patients have uncontrolled blood pressure (BP) determined as > 140 mmHg and >
[5,6]
90 mmHg for office systolic and diastolic BP respectively . Recent observational and clinical studies have
shown that target organ damages were more frequently detected in uncontrolled hypertensive individuals
[5,7]
and resistant hypertensive patients than those who had fully controlled hypertension . Nevertheless, it
was found that the endothelial dysfunction may be a result of direct vasculature damage due to the effect
[7,8]
of cardiovascular (CV) risk factors and the natural evolution of hypertension . Additionally, endothelial
dysfunction is strongly associated with not only a very high CV risk profile, but a higher rate of CV events
[8]
in hypertensive individuals . Although endothelial dysfunction emerges as a primary cause of essential
hypertension and its evolution understanding the whole components involving in the pathophysiology
of regulation of vascular structure and function become of great importance for the prediction of target
[9]
organ damage and risk stratification . The investigation of clinical significance of the role of endothelial
dysfunction in developing and progression of essential hypertension could open novel perspectives for
targeting the treatment of hypertension.

The pathophysiological mechanisms of endothelial dysfunction development involve several factors
contributing to various causes of loss of normal vascular function and structure. The experimental models
of essential hypertension have confirmed that genetic/epigenetic factors interacting with traditional
(smoking, dyslipidemia, insulin resistance, diabetes mellitus) and specific (hyperuricemia, vitamin D
deficiency, elevated homocysteine levels, inflammation, oxidative stress, hypercoagulation) CV risk factors
and surrounding environment may regulate vascular reparation through synthetiz ing and release of various
spectra of vasoactive substances including nitric oxide (NO), involving cell mechanisms and attenuation of
synthesis of pro-inflammatory cytokines, chemokines, and reactive oxygen species (ROS) [10-14] . Consequently,
vascular resident cells and circulatig progenitor cells with different origin and phenotypes (mononuclear
and endothelial progenitor cells) may play a pivotal role in vascular repair, improving vascular integrity and
[15]
function . Finally, the imbalance between vasculature damage and vascular reparation capability could be
considered as an independent factor contributing to endothelial function and vasculature structure that are
central players in vascular tone regulation and target organ damage prevention [16-19] . The aim of this review
is to update the current evidence of the role of endothelial progenitor cell dysfunction in impaired vascular
reparation and CV risk in hypertension.

DEFINITION OF ENDOTHELIAL PROGENITOR CELLS
[20]
The pioneer work provided by Asahara et al. (1997) first reported about existing populations of circulating
cells with impressive angiogenic capacities. Using animal models of ischemia the authors found sites of
active angiogenesis with incorporation into its putative progenitor endothelial cells or angioblasts, which
were further isolated from peripheral blood of animals and humans by magnetic bead selection on the basis
of cell surface antigen expression [20,21] . In vitro these cells expanded and committed to form an endothelial
lineage in colonies in culture, and in vivo after transplantation these cells have been incorporated into
cores of active neovascularization demonstrating an ability to attenuate angiogenesis and vascular function
through differentiation into mature microvascular endothelial cells [22,23] . It has been postulated that these
cells called endothelial progenitor cells (EPCs) may origin from bone marrow stem cells and human
umbilical cord blood and that they may mobilize and migrate from bone marrow, differentiate into mature
endothelial cells and probably smooth muscle cells of vessels, as well as synthase and release a wide range of
active molecules and growth factors [vascular endothelial growth factor (VEGF), fibroblast growth factor,
granulocyte-macrophage colony-stimulating factor] that modulate vasculogenesis and improve vascular
integrity [24,25] .

DETERMINATION OF IMMUNE PHENOTYPES AND FUNCTIONALITIES OF EPCS
Early attempts to verify the population of EPCs were based on determination of molecular characteristics
especially when flow cytometry technique was being implemented. To improve the understanding in im-